The role of glucagon-like peptide-1 receptor agonists in cancer therapy-related cardiovascular disease: a meta-analysis

To the Editor: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have emerged as a cornerstone in the management of type 2 diabetes (T2D) and obesity, offering both glycaemic control and significant weight reduction. Beyond these metabolic benefits, cardiovascular outcome trials have demonstrated that GLP-1RA also reduce major adverse cardiovascular events (MACE) and improve clinical outcomes in patients with T2D and/or obesity.1 In addition, the GLP-1RA semaglutide and the dual GLP-1RA and gastric inhibitory polypeptide (GIP) agonist tirzepatide improve symptoms and cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF) and obesity.2,3 These broad benefits of GLP-1RA have been attributed to their multiple mechanisms of action as well as to their potential pleiotropic properties including anti-inflammatory, anti-apoptotic and endothelial-protective actions.1 The cardiometabolic benefits and the potential pleiotropic properties of GLP-1RA provide a compelling rationale to explore their role in other disease states, including cancer. It has thus been postulated that GLP-1RA may mitigate the risk of malignancies associated with diabetes or obesity.4 Τhis hypothesis has been supported by observational studies and meta-analyses showing a reduced risk of certain cancer types, such gastrointestinal, endometrial, breast and prostate cancer, in patients with diabetes and/or obesity.5 However, the available evidence remains observational and partially conflicting.